Akademik Veri Yönetim Sistemi
The 27th Congress of the European Hematology Association , Vienna, Avusturya, 9 - 12 Haziran 2022, cilt.6, sa.1369, ss.2398-2399
Background: Endothelial damage is considered to be the major underlying mechanism in the physiopathogenesis of transplant related complications including graft versus host disease (GVHD), thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS) and sepsis. A novel scoring index, Endothelial Activation and Stress Index (EASIX), is a simple method consisting of endothelial activation parameters, which was indicated to predict GVHD and posttransplant survival. Similarly, modified EASIX (mEASIX) is a marker of endothelial dysfunction and has been shown to be associated with the development of cytokine release syndrome after CAR-T cell therapy. In this study, we investigated the role of EASIX and mEASIX scores in the prediction of transplant related complications and survival in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT).
Methods: A total of 398 alloHCT recipients [median age: 43(17-71) years; male/female: 243/155] were included in this retrospective study. EASIX [lactate dehydrogenase (U/L) x creatinine (mg/dl) / platelets (109/L)] and mEASIX [lactate dehydrogenase (U/L) x C reactive protein (CRP) (mg/dl) / platelets (109/L)] scores were calculated on days -7, 0, +3 and +7. Statistical analysis was performed based on log2 transformed values. Primary outcomes of the study were considered to be overall survival (OS), non relapse mortality (NRM), day30 and day100 mortality, whereas secondary outcomes were assessed to be GVHD, TMA, SOS and early posttransplant toxicities. Patient and transplant characteristics are summarized in Table 1.
Results: Median follow-up time was 573.5 (4-3877) days. Probability of OS was estimated to be 35.1% (1343 ± 351.7; 95% CI: 653.6-2032.3), while the probabilities of day30 mortality, day100 mortality and NRM were 6%, 12.5% and 49% respectively. In multivariate analysis EBMT score (p=0.026, HR: 1.177; 95% CI: 1.019-1.359), CRP (p=0.033, HR: 1.004; 95% CI: 1.000-1.008), EASIX-7 (p=0.042, HR: 0.182; 95% CI: 0.035-0.941) and mEASIX-7 (p=0.016, HR: 2.668; 95% CI: 1.202-5.924) were found to have significant impact on OS. The predictive effect of mEASIX-7 was confirmed for day30 mortality (p=0.038; HR: 1.7; 95% CI: 1.030-2.805). A positive correlation was demonstrated between mEASIX-7 and SOS (p=0.013; r=0.249). On the other hand, mEASIX+7 was found to have a significant impact on the development of engraftment syndrome (p=0.028; HR: 1.403; 95% CI: 1.038-1.896), EASIX+3 on TMA (p=0.027; HR: 2.361; 95% CI: 1.100-5.066) and mEASIX0 on TMA (p=0.011; HR: 2.209; 95% CI: 1.199-4.068). EASIX0 (p=0.015; HR: 0.369; 95% CI: 0.165-0.825), mEASIX0 (p=0.035; HR: 1.547; 95% CI: 1.031-2.321) and mEASIX+7 (p=0.029; HR: 1.678; 95% CI: 1.055-2.668) had a statistically significant impact on the development of diarrhea. Based on the optimal cutoff value of mEASIX-7 for the prediction of day30 mortality, which was determined to be 2.71 [AUC: 0.747 (0.599-0.896); p=0.021], the study group was divided into two subgroups as low-mEASIX-7 and high-mEASIX-7 groups. Probability of OS was significantly higher in the low-mEASIX-7 group compared to high-mEASIX-7 group (37% vs 25.2%; p=0.008; HR: 2.057; 95% CI: 1.208-3.504) (Figure 1). Day30 mortality (2.9% vs 19.4%; p=0.017; HR: 7.028; 95% CI: 1.418-34.836) and day100 mortality (9% vs 33%; p=0.004; HR: 4.469; 95% CI: 1.619-12.336) were significantly lower in the low-mEASIX-7 group. Furthermore, the probability of NRM was significantly lower in the low-mEASIX-7 group compared to high-mEASIX-7 group (44.8% vs 61.4%; p=0.005; HR: 2.551; 95% CI: 1.318-4.941).
Conclusions: Pretransplant risk assessment is essential to
guide the mainstays of the transplant procedure and optimize supportive care
measures. In consideration with the basic role of endothelial activation in the
development of life threatening complications of alloHCT, mEASIX-7
is indicated to have a predictive prognostic impact on survival and transplant
related complications.